Global profiling of protein lipidation using chemical proteomic technologies

Abstract

Protein lipidation is unique amongst post-translational modifications (PTMs) in enabling direct interaction with cell membranes, and is found in every form of life. Lipidation is important in normal function and in disease, but its intricate interplay with disease context presents a challenging for drug development. Global whole-proteome profiling of protein lipidation lies beyond the range of standard methods, but is well-suited to metabolic tagging with small 'clickable' chemical reporters that do not disrupt metabolism and function; chemoselective reactions are then used to add multifunctional labels exclusively to tagged-lipidated proteins. This chemical proteomic technology has opened up the first quantitative whole-proteome studies of the known major classes of protein lipidation, and the first insights into their full scope in vivo.